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J Cancer Res Clin Oncol. 2019 Jan;145(1):65-76. doi: 10.1007/s00432-018-2761-y. Epub 2018 Oct 24.

FUT4 is involved in PD-1-related immunosuppression and leads to worse survival in patients with operable lung adenocarcinoma.

Liu C1,2,3, Li Z1,2, Wang S1,2, Fan Y1,2, Zhang S1,2, Yang X4, Hou K1,2, Tong J5, Hu X6, Shi X1,2, Wang X1,2, Liu Y1,2, Che X7,8, Qu X9,10.

Author information

1
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China.
2
Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China.
3
Medical Research Center, The Fourth Hospital of China Medical University, Shenyang, 110032, China.
4
Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
5
Drug Clinical Trial Institution, The First Hospital of China Medical University, Shenyang, 110001, China.
6
Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, China.
7
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China. xfche@cmu.edu.cn.
8
Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. xfche@cmu.edu.cn.
9
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China. xiujuanqu@yahoo.com.
10
Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. xiujuanqu@yahoo.com.

Abstract

PURPOSE:

As an important glycosyltransferase, fucosyltransferase IV (FUT4) is abnormally upregulated in different types of cancers, but its clinical role remains inexplicit. This work aimed to determine the predictive ability of FUT4 in lung adenocarcinoma (LUAD) after curative resection, as well as to explore the role of a possible FUT4 molecular mechanism on LUAD malignant behavior.

METHODS:

A total of 273 LUAD patients after curative resection with complete clinicopathological and RNAseq data from The Cancer Genome Atlas (TCGA) cohort were collected. Correlation of FUT4 with overall survival (OS) was analyzed based on TCGA and further validated by online "Kaplan-Meier Plotter" database and IHC in 70 LUAD patients recruited in the First Hospital of China Medical University cohort. Multivariate Cox regression analysis and 1000 bootstrapping were performed to verify the predictive value of FUT4. Gene set enrichment assay (GSEA) was performed to investigate the biological characteristics. Correlation between PD-1 and FUT4 was analyzed based on TCGA cohort and validated by IHC on cohort from our hospital.

RESULTS:

Increased FUT4 expression led to reduced overall survival (OS) of LUAD patients based on TCGA (p = 0.006 and 0.001 for dichotomous and trichotomous modeling, respectively) and externally validated in KMPLOTTER (p = 0.01) and by IHC based on cohort from our hospital (p = 0.005 and p = 0.019 for dichotomous and trichotomous modeling, respectively). FUT4 overexpression was an independent high risk factor for OS along with advanced pT stage and pTNM stage (p = 0.001, p = 0.037, and p < 0.001, respectively). GSEA revealed that FUT4 overexpression might correlate with shortened survival of LUAD patients by promoting cell proliferation via ERBB signaling, and suppressing immune response-related pathways. FUT4 expression positively correlated with PD-1 in TCGA (p = 0.026) and validated by IHC on cohort from our hospital (p = 0.029).

CONCLUSIONS:

Increased FUT4 expression led to reduced OS in operable LUAD. FUT4 showed significant correlation with immune response and PD-1 expression.

KEYWORDS:

FUT4; Lung adenocarcinoma; PD-1; Prognosis; Survival

PMID:
30357521
DOI:
10.1007/s00432-018-2761-y
[Indexed for MEDLINE]

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